Age-associated decay of intercellular interactions impairs the cells' capacity to tightly associate within tissues and form a functional barrier. This barrier dysfunction compromises organ physiology and contributes to systemic failure. The actin cytoskeleton represents a key determinant in maintaining tissue architecture. Yet, it is unclear how age disrupts the actin cytoskeleton and how this, in turn, promotes mortality. Here, we show that an uncharacterized phosphorylation of a low-abundant actin variant, ACT-5, compromises integrity of the C. elegans intestinal barrier and accelerates pathogenesis. Age-related loss of the heat-shock transcription factor, HSF-1, disrupts the JUN kinase and protein phosphatase I equilibrium which increases ACT-5 phosphorylation within its troponin binding site. Phosphorylated ACT-5 accelerates decay of the intestinal subapical terminal web and impairs its interactions with cell junctions. This compromises barrier integrity, promotes pathogenesis, and drives mortality. Thus, we provide the molecular mechanism by which age-associated loss of specialized actin networks impacts tissue integrity.

中文翻译：

---

次要肌动蛋白变体的年龄发作磷酸化促进肠道屏障功能障碍。

与年龄相关的细胞间相互作用的衰退削弱了细胞在组织内紧密结合并形成功能性屏障的能力。这种屏障功能障碍损害器官生理并导致全身衰竭。肌动蛋白的细胞骨架代表维持组织结构的关键决定因素。然而，尚不清楚年龄如何破坏肌动蛋白的细胞骨架，以及反过来又如何提高死亡率。在这里，我们显示低丰度肌动蛋白变体ACT-5的未表征的磷酸化，损害线虫肠屏障的完整性并加速发病机理。与年龄有关的热休克转录因子HSF-1的丢失破坏了JUN激酶和蛋白质磷酸酶I的平衡，从而增加了其肌钙蛋白结合位点内的ACT-5磷酸化。磷酸化的ACT-5会加速肠顶下末端网的腐烂，并削弱其与细胞接头的相互作用。这损害了屏障的完整性，促进了发病机理，并提高了死亡率。因此，我们提供了与年龄相关的专业肌动蛋白网络的丧失影响组织完整性的分子机制。